This is a competing renewal application for the New England Consortium Node (NECN), led by Kathleen Carroll, Ph.D., of Yale and Roger Weiss, M.D., of Harvard. The NECN has a track record of outstanding productivity in the Clinical Trials Network (CTN), with leadership of 4 highly successful trials, high levels of study participation, excellent recruitment and retention, and 64 peer-reviewed publications from CTN trial data during the current funding period. NECN investigators have first-authored all 3 of the most highly-cited CTN publications and all 4 CTN publications cited most often per year. The overarching goal of the NECN is to develop effective and sustainable interventions for substance use disorders that can be delivered in multiple healthcare settings, addressing substance use in all its diversity. Achieving this goal will entail 1) building on single-site efficacy trials to conduct multi-site effectiveness studies of promising interventions; 2) improving interventions with promising but modest results to date; and 3) developing innovative approaches for prevalent problems with no clearly established standard of care, or with suboptimal results in early studies (e.g., screening and brief intervention for drug use in primary care). To address these goals, the NECN has added 1) local, regional, and national hospital-based and primary care networks that cover millions of individuals, and 2) investigators from 7 New England universities who have conducted seminal work in addiction medicine and innovative technology (Drs. Fiellin, Higgins, Marsch, O?Connor, Saitz, Samet). The NECN research agenda demonstrates its capacity to develop and implement novel approaches to improve treatment for substance users wherever they contact the healthcare system. Proposed studies build on the previous work of NECN investigators and include, among others: 1. Screening and brief intervention (SBI) vs. repeated BIs vs. computer-based cognitive-behavioral therapy for risky drug use in primary care (Saitz, Carroll); 2. Financial incentives for pregnant smokers in obstetrical practice (Higgins); 3. Buprenorphine initiation in the emergency department vs. facilitated referral for opioid dependent patients (Fiellin, D'Onofrio); and 4. Use of peer navigators to enhance treatment retention among opioid dependent patients started on buprenorphine during hospitalization (Liebschutz, Stein).